Core H: Down Syndrome Core Project Summary/Abstract Since its inception, the UC Irvine Alzheimer Disease Research Center (ADRC) has included people with Down syndrome (DS) as a central focus of its research mission. Because of the triplication of the APP gene on chromosome 21, individuals with DS accumulate amyloid in the brain over the lifespan. This places people with DS at substantially increased risk for dementia. Yet, the age of symptom onset is variable and there is need for increased understanding of the temporal sequence of events in the AD pathogenesis as well as factors that precipitate dementia and protect against it. This application represents the launch of an independent DS Core in the ADRC, an exciting development that will increase opportunities for the study of DS and AD at UCI and beyond. Establishing a DS Core will facilitate interactions between this and other ADRC Cores, especially new cores being initiated, such as the Biomarker Core, and will enhance opportunities for data sharing. The DS Core will continue to engage in longitudinal research. The Core will expand the population enrolled, including participants as young as 18 years of age, to better elucidate the earliest possible stages of disease. Special emphasis will be placed on developing tools to facilitate multisite DS research, including clinical trials. As always, the expert investigators studying the DS and AD will contribute their unique expertise and experiences to training the next generation of clinicians and scientists. The DS Core will continue to provide unique insights into the understanding of AD.